Functional dissection of human and mouse POT1 proteins.
The single-stranded telomeric DNA binding protein POT1 protects mammalian chromosome ends from the ATR-dependent DNA damage response, regulates telomerase-mediated telomere extension, and limits 5'-end resection at telomere termini. Whereas most mammals have a single POT1 gene, mice have two POT1 proteins that are functionally distinct. POT1a represses the DNA damage response, and POT1b controls 5'-end resection. In contrast, as we report here, POT1a and POT1b do not differ in their ability to repress telomere recombination. By swapping domains, we show that the DNA binding domain of POT1a specifies its ability to repress the DNA damage response. However, no differences were detected in the in vitro DNA binding features of POT1a and POT1b. In contrast to the repression of ATR signaling by POT1a, the ability of POT1b to control 5'-end resection was found to require two regions in the C terminus, one corresponding to the TPP1 binding domain and a second representing a new domain located between amino acids (aa) 300 and 350. Interestingly, the DNA binding domain of human POT1 can replace that of POT1a to repress ATR signaling, and the POT1b region from aa 300 to 350 required for the regulation of the telomere terminus is functionally conserved in human POT1. Thus, human POT1 combines the features of POT1a and POT1b.
Palm
Wilhelm
W
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065-6399, USA.
Hockemeyer
Dirk
D
Kibe
Tatsuya
T
de Lange
Titia
T
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D018345:Mice, Knockout; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011995:Recombination, Genetic; D000089804:Shelterin Complex; D015398:Signal Transduction; D016615:Telomere / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C495876:ACD protein, human; C544060:Acd protein, mouse; D004268:DNA-Binding Proteins; C440849:POT1 protein, human; C507326:POT1 protein, mouse; D011993:Recombinant Fusion Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins